Prenatal Immune Challenge Sensitizes Adult Offspring Against Late Brain Changes in Rats Surviving Sepsis

Early challenges during the prenatal period can induce long-lasting effects in the offspring, including neurological changes. However, emerging evidence suggests that the innate immune system in early life has plasticity and that stimuli applied at the appropriate time and dose during this window can shape long-term immune responses that persist into adulthood. This study aimed to investigate whether prenatal exposure to lipopolysaccharide (LPS) modulates brain changes after sepsis in adult offspring, male and female. Pregnant Wistar rats received an intraperitoneal injection of LPS (100 μg/kg) on gestational day 9.5. In adulthood, offspring were subjected to sepsis induced by cecal ligation and puncture (CLP) or sham surgery, resulting in four experimental groups: saline+sham, LPS+sham, saline+CLP and LPS+CLP. Survival after CLP was monitored and, 10 days later, brain regions (cortex, prefrontal cortex and hippocampus) were collected for cytokine level analysis. Prenatal exposure to LPS improved survival rates. It also increased IL-10 levels in all brain regions and raised IL-6 in the hippocampus of males. These findings suggest that prenatal immune challenge with LPS may confer neuroprotective effects against brain changes induced by severe sepsis in adult offspring.